Dr. Jack West's presentation on highlights in advanced non-small cell lung cancer from ASCO 2014, focusing on new agents ramucirumab and necitumumab for broad NSCLC populations, crizotinib and ceritinib for ALK-positive NSCLC, EGFR inhibitor-options of afatinib and bevacizumab added to erlotinib for first line treatment of EGFR mutation-positive NSCLC, and AZD9291 or CO1686 for EGFR mutation-positive patients with acquired resistance.
10 Key ASCO 2014 Presentations in Lung CancerH. Jack West
Dr. Jack West offers a list of 10 of the most important, timely abstract presentations in lung cancer, both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), at the annual ASCO 2014 conference.
Acquired Resistance to Targeted Therapy in EGFR and ALK-Positive Lung Cancer:...H. Jack West
This is a presentation I did for a meeting on new general management of acquired resistance in 2014, including the concept of local therapy for limited progression, and new treatment approaches and new agents for this setting. It features discussion of several of the most important trials.
10 Key ASCO 2014 Presentations in Lung CancerH. Jack West
Dr. Jack West offers a list of 10 of the most important, timely abstract presentations in lung cancer, both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), at the annual ASCO 2014 conference.
Acquired Resistance to Targeted Therapy in EGFR and ALK-Positive Lung Cancer:...H. Jack West
This is a presentation I did for a meeting on new general management of acquired resistance in 2014, including the concept of local therapy for limited progression, and new treatment approaches and new agents for this setting. It features discussion of several of the most important trials.
Lung cancer is a major cause of cancer deaths with approximately 80% of cases accounting to nonsmall cell lung cancer (NSCLC) . In NSCLC target therapy, epidermal growth factor receptor (EGFR) is a promising candidate.
Co-Chairs Roy S. Herbst, MD, PhD, and Lecia V. Sequist, MD, MPH, prepared useful Practice Aids pertaining to EGFR-mutated lung cancer for this CME activity titled “New Milestones and Changing Standards of Care in EGFR-Mutated NSCLC: Expanding the Benefits of Genomic Testing and EGFR-Targeted Therapy to Early-Stage Lung Cancer.” For the full presentation, downloadable Practice Aids, and complete CME information, and to apply for credit, please visit us at http://bit.ly/36aVo39. CME credit will be available until March 8, 2022.
Roy H. Decker, MD, PhD; Kristin Higgins, MD; and Jyoti D. Patel, MD, prepared useful practice aids pertaining to immunotherapies in lung cancer for this CME/MOC activity titled “NSCLC Tumor Board: Navigating the Evolving Role of Immunotherapy in Multimodal Management of Locally Advanced and Early-Stage Lung Cancer.” For the full presentation, monograph, complete CME/MOC information, and to apply for credit, please visit us at http://bit.ly/2mFfEWE. CME/MOC credit will be available until October 22, 2020.
Jessica Donington, MD, Natasha Leighl, MD, MMSc, FRCPC, FASCO, and Brendon Stiles, MD, prepared useful practice aids pertaining to the role of immunotherapy in lung cancer for this CME/MOC/CNE activity titled, "The Expanding Role of Immunotherapy in Locally Advanced and Earlier Stages of Lung Cancer: Rationale, Current Evidence, Key Trials, and Implications for Thoracic Surgeons." For the full presentation, monograph, complete CME/MOC/CNE information, and to apply for credit, please visit us at http://bit.ly/2WibbtU. CME/MOC/CNE credit will be available until June 16, 2020.
Lung cancer is a major cause of cancer deaths with approximately 80% of cases accounting to nonsmall cell lung cancer (NSCLC) . In NSCLC target therapy, epidermal growth factor receptor (EGFR) is a promising candidate.
Co-Chairs Roy S. Herbst, MD, PhD, and Lecia V. Sequist, MD, MPH, prepared useful Practice Aids pertaining to EGFR-mutated lung cancer for this CME activity titled “New Milestones and Changing Standards of Care in EGFR-Mutated NSCLC: Expanding the Benefits of Genomic Testing and EGFR-Targeted Therapy to Early-Stage Lung Cancer.” For the full presentation, downloadable Practice Aids, and complete CME information, and to apply for credit, please visit us at http://bit.ly/36aVo39. CME credit will be available until March 8, 2022.
Roy H. Decker, MD, PhD; Kristin Higgins, MD; and Jyoti D. Patel, MD, prepared useful practice aids pertaining to immunotherapies in lung cancer for this CME/MOC activity titled “NSCLC Tumor Board: Navigating the Evolving Role of Immunotherapy in Multimodal Management of Locally Advanced and Early-Stage Lung Cancer.” For the full presentation, monograph, complete CME/MOC information, and to apply for credit, please visit us at http://bit.ly/2mFfEWE. CME/MOC credit will be available until October 22, 2020.
Jessica Donington, MD, Natasha Leighl, MD, MMSc, FRCPC, FASCO, and Brendon Stiles, MD, prepared useful practice aids pertaining to the role of immunotherapy in lung cancer for this CME/MOC/CNE activity titled, "The Expanding Role of Immunotherapy in Locally Advanced and Earlier Stages of Lung Cancer: Rationale, Current Evidence, Key Trials, and Implications for Thoracic Surgeons." For the full presentation, monograph, complete CME/MOC/CNE information, and to apply for credit, please visit us at http://bit.ly/2WibbtU. CME/MOC/CNE credit will be available until June 16, 2020.
During the event, our team provided a series of short, sharp presentations which aimed at bringing our partners up to speed with our national and international work - from major events to inward investment - and highlighting opportunities for them and their businesses.
Partners also heard from VisitEngland chief executive James Berresford, about the national tourism landscape, the growth strategy for tourism and major new funding programmes which are underway and set to benefit our region this year.
NewcastleGateshead Initiative Partner Update Meeting October 2015newcastlegateshead
Slides from NewcastleGateshead Initiative's Partner Update Meeting at St Nicholas Cathedral on 8 October 2015, including presentations on the Eleven Arches project and NewcastleGateshead's bid to host the 2019 World Transplant Games.
David R. Jones, MD, and Roy S. Herbst, MD, PhD, prepared useful practice aids pertaining to lung cancer for this CME activity titled "Turning Tides in Targeted Therapy for Early-Stage EGFR-Mutated NSCLC: Latest Data and Practical Guidance for Thoracic Surgeons and the Multidisciplinary Team on the Emerging Role of EGFR-Targeted Therapy in Resectable Lung Cancer." For the full presentation, complete CME information, and to apply for credit, please visit us at https://bit.ly/2PSVELG. CME credit will be available until November 9, 2021.
Chair & Presenter, David R. Jones, MD, and Nathan A. Pennell, MD, PhD, FASCO, prepared useful Practice Aids pertaining to NSCLC for this CME/MOC activity titled “Adjuvant EGFR-Targeted Therapy as a Game Changer: How to Implement New Standards of Care in Multimodal Management of Stage I-III EGFR-Mutated NSCLC.” For the full presentation, downloadable Practice Aids, and complete CME/MOC information, and to apply for credit, please visit us at https://bit.ly/3mFfjji. CME/MOC credit will be available until December 2, 2022.
Moving Beyond the Hype: 3 Key Steps for Personalized Cancer MedicineH. Jack West
The concept of personalized or precision medicine is hot enough that President Obama is launching initiatives for it, but how close is it to moving beyond hype?
Here are 3 key steps we need to attain to know that personalized medicine, particularly in the world of cancer care, isn't just delivering false hope for most patients.
Transitioning Survival from Months to Years in Advanced Non-Small Cell Lung C...H. Jack West
Dr. Jack West reviews the evolution of new treatment options for advanced NSCLC that have steadily improved survival. This progress has been incremental but now means that an ever-growing proportion of patients with advanced NSCLC have a realistic promise of potentially living several years after their diagnosis and the start of treatment. Note that this presentation does not address advances in immunotherapy, which were covered in a separate talk at the same conference at which Dr. West delivered this presentation.
What is the value of maintenance therapy in advanced NSCLC, and who should ge...H. Jack West
Dr. Jack West reviews the rationale for maintenance therapy in advanced NSCLC, what the evidence shows about its value, the limitations, and thoughts on which patients should or should not pursue it.
50 Shades of Cancer Progression: The Continuum of Progression & How We Decide...H. Jack West
Dr. Jack West reviews the importance of assessing the degree of progression when interpreting whether to change treatment of a cancer. It is important to ask not only whether a cancer has progressed, but HOW it has done so, and how much?
Key Clinical Implications of how a Cancer EvolvesH. Jack West
Cancer adapts and evolves over time and under the selective pressure of systemic treatment, becoming increasingly resistant over time. This brief slidedoc fo summarizes key points in how cancer adaptation leads to resistance and changes our treatment recommendations.
Treating Invisible Disease: How the Probability of Disease We Can't See Chang...H. Jack West
A brief slidedoc that reviews why we focus on both the cancer we can see and the potential cancer we can't when we shape our treatment recommendations in lung cancer and many other cancers.
Changes Afoot: Changing Relationships between Engaged Patients and Docs in Ca...H. Jack West
Discussion of how online patient communities and social media are changing relationships between engaged patients and oncologists, improving quality of cancer care.
West Immunotherapy, Vaccines for Lung Cancer Mage-A3, Stimuvax, and LucanixH. Jack West
Update of results and current clinical trials of vaccines for lung cancer, including MAGE-A3, Stimuvax, and Lucanix for stage I-III non-small cell lung cancer. @JackWestMD, @CancerGRACE cancerGRACE.org
West egfr mutation acquired resistanceH. Jack West
Review by Dr. H. Jack West of current understanding of mechanisms behind and emerging treatment options for patients with advanced NSCLC with acquired resistance to EGFR tyrosine kinase inhibitors after a good initial response.
Dr. Jack West Oncology 2.0, to WA AG's OfficeH. Jack West
Dr. H. Jack West, medical oncologist and Founder/CEO of Global Resource for Advancing Cancer Education (GRACE, www.CancerGRACE.org), spoke to WA state Attorney General's office about the changing landscape of cancer care and how the internet and specifically online patient communities and education will become disruptive in changing the patient/physician dynamic.
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
263778731218 Abortion Clinic /Pills In Harare ,ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group of receptionists, nurses, and physicians have worked together as a teamof receptionists, nurses, and physicians have worked together as a team wwww.lisywomensclinic.co.za/
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
CDSCO and Phamacovigilance {Regulatory body in India}NEHA GUPTA
The Central Drugs Standard Control Organization (CDSCO) is India's national regulatory body for pharmaceuticals and medical devices. Operating under the Directorate General of Health Services, Ministry of Health & Family Welfare, Government of India, the CDSCO is responsible for approving new drugs, conducting clinical trials, setting standards for drugs, controlling the quality of imported drugs, and coordinating the activities of State Drug Control Organizations by providing expert advice.
Pharmacovigilance, on the other hand, is the science and activities related to the detection, assessment, understanding, and prevention of adverse effects or any other drug-related problems. The primary aim of pharmacovigilance is to ensure the safety and efficacy of medicines, thereby protecting public health.
In India, pharmacovigilance activities are monitored by the Pharmacovigilance Programme of India (PvPI), which works closely with CDSCO to collect, analyze, and act upon data regarding adverse drug reactions (ADRs). Together, they play a critical role in ensuring that the benefits of drugs outweigh their risks, maintaining high standards of patient safety, and promoting the rational use of medicines.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of the physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Basavarajeeyam is a Sreshta Sangraha grantha (Compiled book ), written by Neelkanta kotturu Basavaraja Virachita. It contains 25 Prakaranas, First 24 Chapters related to Rogas& 25th to Rasadravyas.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Adv. biopharm. APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMSAkankshaAshtankar
MIP 201T & MPH 202T
ADVANCED BIOPHARMACEUTICS & PHARMACOKINETICS : UNIT 5
APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMS By - AKANKSHA ASHTANKAR
Adv. biopharm. APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMS
Best of ASCO Metastatic Non-Small Cell Lung Cancer
1. Best of ASCO 2014:
Highlights in Metastatic
Non-Small Cell Lung Cancer
Howard (Jack) West, MD
@JackWestMD
Swedish Cancer Institute
Seattle, WA
Best of ASCO 2014
Seattle, WA
2. Learning Objectives
• Determine whether evidence on necitumumab and
ramucirumab for broad NSCLC populations are sufficient to
modify current treatment standards
• Evaluate treatment options of crizotinib and ceritinib for
ALK-positive advanced NSCLC
• Compare utility of various EGFR TKI-based options as first
line treatment of advanced EGFR mutation-positive NSCLC
• Recognize efficacy of both AZD9291 and CO1686 in
treating acquired resistance to EGFR TKIs (*T790M-
positive)
4. SQUIRE: Chemotherapy +/- Necitumumab
for First Line Adv Squamous NSCLC
Adv squamous
NSCLC
Treatment-naïve
N = 1093
R
A
N
D
O
M
I
Z
E
Cisplatin/Gemcitabine
+ Necitumumab
up to 6 cycles
Primary endpoint: OS
• Necitumumab (Neci) (IMC-11F8) is a human IgG1 anti-EGFR
monoclonal antibody
Cisplatin/Gemcitabine
up to 6 cycles
Maintenance
neci until
progression
Cisplatin 75 mg/m2 IV day 1 q21 days
Gemcitabine 1250 mg/m2 IV days 1, 8 q21 days
Necitumumab 800 mg/kg IV days 1, 8 q21 days
Thatcher, A#8008
7. SQUIRE: FLEX Redux? (Re-FLEX?)
SQUIRE FLEX
• Extremely similar agent; extremely similar results
– cetuximab has had negligible impact on NSCLC management
• Highlights distinction between statistical & clinical significance
Pirker, Lancet 2009Thatcher, A#8008
8. REVEL: Docetaxel +/- Ramucirumab as
Second Line Therapy for Adv NSCLC
Adv NSCLC
(any histology)
Prior platinum-
based chemo
Prior bev allowed
N = 1253
R
A
N
D
O
M
I
Z
E
Docetaxel 75 mg/m2 +
Ramucirumab 10 mg/kg
IV Q21 days
Docetaxel 75 mg/m2 +
Placebo
IV Q21 days
Primary endpoint: OS
Treat until PD
or prohibitive
toxicity
• Ramucirumab (RAM) is a human IgG1 monoclonal antibody,
specifically binding to the extracellular domain of VEGFR-2
• Approved in previously treated gastric cancer
Perol, A#LBA-8006
11. Half Empty or Half Full?
• 1.4 mo increase in OS isn’t much
• Cost: about $7K/treatment
• But options improving OS >2nd line
are very limited, especially for
squamous NSCLC
Optimistic oncologist perspective
• Whether adding new agent with some increased toxicity
and additional significant cost is “worth it” for 1.4 mo
improvement in median OS is your judgment
• Not a clear change in standard of care
12. (Not Very) Old and New
Agents for ALK-Positive
Advanced NSCLC
13. PROFILE 1014: First-Line Crizotinib vs.
Chemo in ALK-Positive Adv NSCLC
• Crizotinib has significant activity, RR 60-65%, in previously
treated ALK+ NSCLC, & PFS 7.7 mo vs. 3.0 months
compared with 2nd line chemo (Shaw, ESMO 2012, A#2862)
• Though largely presumed to be superior to first line chemo
in ALK-positive NSCLC, this hasn’t been prospectively
demonstrated
Advanced
NSCLC ALK+
No Prior Rx
N= 343
R
A
N
D
Crizotinib
Cisplatin/Pemetrexed or
Carboplatin/Pemetrexed
Primary endpoint: PFS
1: 1
Mok, A#8002
19. Activity of Ceritinib in ALK+ NSCLC
Endpoint Criz-Naïve
(N = 83)
Criz-Refractory
(N = 163)
Response Rate 66% 55%
12-mo Prog-Free Survival 61% 28%
Median Time from Dx to
Ceritinib
8.1 mo 21.2 mo
Disease Control, Brain Mets 70% 75%
• Modestly higher RR, longer responses in crizotinib-
naïve patients
Kim, A#8003
20. Toxicity Challenges with Ceritinib
• Greater than with crizotinib
• Dose reduction – 59% (!)
– Increased ALT/AST, nausea, diarrhea, vomiting
• Discontinuation due to adverse effects – 10%
– Pneumonia, ILD/pneumonitis, decreased appetite
• Oncologists need to know to dose-reduce early
– 750 mg daily may be more than needed
Kim, A#8003
21. Timing of Ceritinib?
Presented by: H. Jack West
• Approval is for crizotinib-refractory and crizotinib-intolerant
patients with ALK rearrangement
• Should it be used earlier?
ALK+
No Prior Rx
N= 348
R
A
N
D
Ceritinib
Cisplatin/Pemetrexed or
Carboplatin/PemetrexedPrimary endpoint: PFS
Trial in
development
ALK+
No Prior Rx
R
A
N
D Ceritinib
Crizotinib
Primary endpoint: OS
Trial
we need
Ceritinib
Chemo or MD choice
23. LUX Lung-3, LUX Lung-6 Trials
EGFR Mut’n Pos
Advanced NSCLC
No Prior Rx
N= 345
Global
R
A
N
D
Afatinib 40 mg PO daily
until progression
Cisplatin/Pemetrexed Q21d
up to 6 cycles
Primary endpoint: PFS
Sequist, JCO 2013LUX Lung-3
R
A
N
D
Afatinib 40 mg PO daily
until progression
Cisplatin d1, Gemcitabine d1,8 q21d
up to 6 cycles
Wu, Lancet 2014
EGFR Mut’n Pos
Advanced NSCLC
No Prior Rx
N= 364
Asia
Primary endpoint: PFS
LUX Lung-6
2:1
2:1
27. Differences in Efficacy of Gefitinib/ Erlotinib:
Exon 19 Del vs. L858R
OSPFS
Jackman,
Clin Cancer Res,
2006
Riely,
Clin Cancer Res,
2006
OS
28. Treatment after Progression on First Line
Therapy (Del 19 and L858R only)
LUX-Lung 3 LUX-Lung 6
Afatinib
(n=203)
Pem/Cis
(n=104)
Afatinib
(n=216)
Gem/Cis
(n=108)
Discontinued treatment, n (%) 184 (100) 104 (100) 194 (100) 108 (100)
Subsequent systemic therapy, n (%)† 144 (78) 88 (85) 123 (63) 70 (65)
Chemotherapy, n (%) 131 (71) 49 (47) 114 (59) 29 (27)
EGFR TKI therapy, n (%)
Erlotinib
Gefitinib
Afatinib
AZD9291
Dacomitinib
Icotinib
EGFR TKI combinations
81 (44)
61 (33)
28 (15)
2 (1)
2 (1)
–
–
5 (3)
78 (75)
46 (42)
44 (42)
7 (7)
1 (1)
1 (1)
–
9 (9)
50 (26)
21 (11)
19 (10)
–
–
–
11 (6)
5 (3)
61 (56)
22 (20)
39 (36)
–
–
–
3 (3)
3 (3)
Other systemic therapy±, n (%) 5 (3) 2 (2) 3 (2) 4 (4)
Radiotherapy, n (%) 32 (17) 21 (20) 4 (2) 0 (0)
†Collection of data on subsequent therapies still ongoing.
± include investigational agents, monoclonal antibodies, non-EGFR targeting protein kinase inhibitors etc
Yang, A#8004
29. Treatment after Progression on First Line by
Country’s Reimbursement*
Countries with universal
reimbursement policies**
Countries without
universal reimbursement
policies***
Afatinib
(n=144)
Chemo
(n=75)
Afatinib
(n=275)
Chemo
(n=137)
Discontinued treatment, n (%) 127 (100) 75 (100) 251 (100) 137 (100)
Subsequent systemic therapy, n (%) 112 (88) 69 (92) 158 (63) 89 (65)
Chemotherapy, n (%) 103 (81) 35 (47) 142 (57) 43 (31)
EGFR TKI, n (%) 76 (60) 68 (91) 55 (22) 71 (52)
Other, n (%) 5 (4) 2 (3) 3 (1) 4 (3)
Radiotherapy, n (%) 27 (22) 18 (24) 9 (4) 3 (2)
*Determined by presence or absence of a national reimbursement policy in effect throughout the period of trial conduct:
**Main countries contributing : Japan, Taiwan, Korea, Germany, France, Australia, UK, Belgium
***Main countries contributing : China, Thailand, Russia, the Philippines, Malaysia
Yang, A#8004
30. Impact of subsequent EGFR TKIs on OS:
exploratory analyses by category of EGFR TKI
reimbursement policy in country of residence*
Population % received
TKI after 1st
line chemo
HR (95% CI)
Common
mutations
HR (95% CI)
Del19
HR (95% CI)
L858R
Combined LL3/6 population
(n=631)
66% 0.81
(0.66–0.99)
0.59
(0.45–0.77)
1.25
(0.92–1.71)
Countries with universal
reimbursement policies**
(n=219)
91% 0.71
(0.49–1.02)
0.50
(0.31–0.81)
1.14
(0.64–2.03)
Countries without universal
reimbursement policies***
(n=412)
52% 0.85
(0.66–1.08)
0.59
(0.42–0.82)
1.32
(0.91–1.92)
Japan
(n=77)
100% 0.57
(0.29–1.12)
0.34
(0.13–0.87)
1.13
(0.40–3.21)
*Determined by presence or absence of a national reimbursement policy in effect throughout the period of trial conduct:
**Main countries contributing : Japan, Taiwan, Korea, Germany, France, Australia, UK, Belgium, Ireland
***Main countries contributing : China, Thailand, Russia, the Philippines, Malaysia
Yang, A#8004
31. Is OS with Afatinib in LUX-Lung 3/6
Superior to That of Other EGFR TKIs?
Med
OS(mo)
WJTOG2 EURTAC3 OPTIMAL4 LUX-
Lung 35
NEJGSG1
Gefitinib Erlotinib Afatinib
1) Maemondo et al. N Engl J Med. 2010;362:2380; 2) Mitsudomi et al. Lancet Oncol. 2010;11:121; 3) Rosell et al.
Lancet Oncol. 2012;13:239; 4) Zhou et al. Lancet Oncol. 2011;12:735; 5) Yang et al. Proc ASCO 2014: A#8004
N=230 N=177
Terminated
early, after
Interim analysis?
N=174 N=165 N=345 N=364
LUX-
Lung 65
EGFR TKI
Chemo
32. Multiple Shots on Goal
• No survival difference for
overall ITT population
• No survival difference for
LUX-Lung trials individually
• Statistical significance is
function of magnitude of
difference & population size
• Pooling two trials and eliminating rare mutations
statistical significance
• Still, OS benefit for Del19 pts is robust, impressive
33. Relevant Comparison for Afatinib
in 2014 is to Other EGFR TKIs
• Is timing of EGFR TKI critical re: crossover?
– L858R population showed PFS benefit but reversal w/OS
– Sequence of therapy may be relevant
• Would other EGFR TKIs show OS benefit if > 700
pts enrolled & results divided by mut’n subtype?
EGFR Mut+
N = 316
(Asia)
R
A
N
D Afatinib daily
Gefitinib daily
Completed July, 2013Primary endpoint: OS
LUX-Lung 7
• Toxicity assessment will also be critical
34. Or is optimal therapy now an
EGFR TKI/bevacizumab
combination?
38. Erlotinib/Bevacizumab vs. Erlotinib for
EGFR Mutation-Positive Adv NSCLC
Adv NSCLC
EGFR Mut’n (exon 19/21)
Treatment-naïve
N = 154
R
A
N
D
Erlotinib 150 mg/day
+ bevacizumab 15 mg/kg IV Q21 days
until progression or prohibitive toxicity
Primary endpoint: PFS
Erlotinib 150 mg/days
until progression or prohibitive toxicity
EB E P
ORR (CR/PR) 69% 64% ns
DCR (CR/PR/SD) 99% 88% 0.018
Kato, A#8005
39. JO25587 PFS in Context of Other Trials
in EGFR Mutation-Positive NSCLC
1. Rosell et al. Lancet Oncol. 2012;13:239; 11. Zhou et al. Lancet Oncol. 2011;12:735; 3. Sequist et al. J Clin Oncol. 2013;31:3327; 4.
Wu et al. Lancet Oncol. 2014;15:213; 5. Kato, Proc ASCO 2014, A#8005
Med
PFS (mo)
EURTAC1 OPTIMAL2 JO25587-
Erlotinib5
JO25587-
Erloti/Bev5
LUX-
Lung-33
LUX-
Lung-64
40. Erlotinib +/- Bevacizumab:
PFS by EGFR mutation type
EB group E group
Median (months) 18.0 10.3
HR 0.41
(95% CI: 0.24–0.72)
EB
E
E
EB
Number at risk
0
1.0
0
40
40 E
EB
Number at risk
EB
E
1.0
0
0
35
37
Time (months)
4 8 122 6 10 14 18 22 2616 20 24 28
38 33 2739 36 29 24 12 5 219 8 2 0
29 22 1235 26 16 9 5 1 09 3 0 0
Time (months)
4 8 122 6 10 14 18 22 2616 20 24 28
31 27 2233 28 24 14 8 3 211 5 2 0
28 17 1231 18 13 12 7 4 19 7 2 0
0.2
0.4
0.6
0.8
PFSprobability
PFSprobability
0.2
0.4
0.6
0.8
Exon 19 deletion Exon 21 L858R
EB group E group
Median (months) 13.9 7.1
HR 0.67
(95% CI: 0.38–1.18)
Kato, A#8005
41. Toxicity Issues with Erlotinib/Bevacizumab
on JO25587
• No unforeseen toxicities or Rx-related deaths
• Grade >3 toxicity 91% vs. 53% (esp. HTN, proteinuria)
• 41% discontinued bevacizumab for adverse effects
– Primarily proteinuria (15%) or hemorrhagic (12%)
• Bevacizumab discontinuation rate 10-15% in
BeTa, ATLAS trials
• Difference?
– Greater toxicity in Japanese population?
– Greater toxicity in EGFR mutation-positive?
– Longer duration of therapy higher risk of ADRs
42. Cost Considerations with
Erlotinib/Bev Combination
Cost/
Month
($USD)
$6,300
$16,700
Erlotinib Erlotinib/
Bevacizumab
Addition of bevacizumab increases cost of first line
treatment by ~$120,000 for 16 treatments
(acquisition cost alone)
43. Is Erlotinib/Bevacizumab the
New Standard of Care for EGFR Mut+?
• Kato: median PFS 16.0 vs. 9.7 mo, HR 0.54
(ECOG 4599: median PFS 6.2 vs. 4.5 mo, HR 0.66)
• My preferred regimen moving forward
• Threshold for clinical confidence ≠ threshold for coverage
• Confirmatory trial needed? Outside of Japan? OS diff?
• Will it be covered?
EGFR Mut+
N = 118
N Amer
R
A
N
D
Erlotinib daily
Erlotinib daily &
Bevacizumab q3wk
Ongoing
(slowly)
Primary endpoint: PFS
ACCRU Trial
PI – T. Stinchcombe
44. Breaking the Impasse for
EGFR Mutation-Positive Patients
with Acquired Resistance
45. Acquired Resistance:
AZD9291 and CO-1686
• The vast majority of patients with an activating EGFR
mutation who respond well to initial EGFR TKI therapy
demonstrate progression several months to years later
• T790M mutation detected in approximately 60% of
patients with acquired resistance
• AZD9291 and CO1686 are mutant selective,
irreversible inhibitors of EGFR with significant anti-
tumor activity in preclinical tumor models with both
EGFR TKI-sensitizing and T790M resistance mutations
with greater wild-type sparing than first generation
EGFR TKIs
46. Best percentage change from baseline in target lesion:
all evaluable patients, escalation and expansion (N=205)
Jänne, A#8009
AZD9291: Response rate*
in overall population( T790M+ and T790M-)
• First patient dosed Mar 6, 2013
• Longest response >9 months ongoing at time of data cutoff
• ORR* = 53% (109/205; 95% CI 46%, 60%); no difference in ORR by race
• Overall disease control rate (CR+PR+SD) = 83% (171/205; 95% CI 78%, 88%)
20 mg 40 mg 80 mg 160 mg 240 mg
N (205) 20 57 61 55 12
ORR 55% 44% 54% 58% 67%
*Includes confirmed responses and responses awaiting confirmation; #represents imputed values. Population: all dosed patients with a
baseline RECIST assessment and an evaluable response (CR, PR, SD, or PD), N=205 (from 232 dosed patients, 27 patients with a current
non-evaluable response are not included). CI, confidence interval; CR, confirmed complete response; ORR, overall response rate;
PD, progressive disease; PR, confirmed partial response; RECIST, Response Evaluation Criteria In Solid Tumors; SD, stable disease
40
20
0
-20
-40
-60
-80
-100
Complete response
#######
Partial response*
Non-response
47. Jänne, A#8009
AZD9291: Response rate* in T790M+
(central test)
• ORR* = 64% (69/107; 95% Cl 55%, 73%) in patients with EGFR T790M+ NSCLC
• Overall disease control rate (CR+PR+SD) = 94% (101/107; 95% CI 88%, 98%)
20 mg 40 mg 80 mg 160 mg 240 mg
N (107) 10 29 34 28 6
ORR 50% 62% 68% 64% 83%
Best percentage change from baseline in target lesion: all evaluable T790M+ patients, Part B
*Includes confirmed responses and responses awaiting confirmation; #represents imputed values
Population: all dosed centrally confirmed T790M+ patients with a baseline RECIST assessment and an evaluable response (CR/PR, SD, or PD),
N=107 (from 120 T790M+ patients; 13 patients with a current non-evaluable response are not included). D, discontinued; QD, once daily
Best percentage change from baseline in target lesion:
T790M+ evaluable patients, expansion cohorts only (N=107)
40 mg QD
80 mg QD
160 mg QD
240 mg QD
20 mg QD
40
20
-20
-40
-60
-80
-100
0
# #
D D
D D
D
D DD D
D D
D D
D D
D
D D
D D
D D
D
48. • ORR* = 22% (11/50; 95% Cl 12%, 36%) in patients with EGFR T790M- NSCLC
• Overall disease control rate (CR+PR+SD) = 56% (28/50; 95% CI 41%, 70%)
20 mg 40 mg 80 mg 160 mg
N (50) 3 17 17 13
ORR 67% 12% 24% 23%
*Includes confirmed responses and responses awaiting confirmation; #represents imputed values
Population: all dosed centrally confirmed T790M- patients with a baseline RECIST assessment and an evaluable response (CR/PR, SD, or PD),
N=50 (from 56 T790M- patients; six patients with a current non-evaluable response are not included)
40 mg QD
80 mg QD
160 mg QD
20 mg QD
# # # #
D D D D
40
20
-20
-40
-60
-80
-100
0
D
D
D
D D
D
D
D D D
D D D D D D D D
D D D
D
D
D
AZD9291: Response rate* in T790M-
(central test)
Jänne, A#8009
49. T790M+ T790M-
68/105
43/69
25/36
11/50
3/28
8/22
Response rate* according to T790M (central test)
status: immediate prior EGFR-TKI,# yes vs no
*Includes confirmed responses and responses awaiting confirmation; #TKI therapy is defined as being immediately
prior if TKI was the last regimen taken prior to the study, with no subsequent therapy. Population: all dosed centrally confirmed
T790M+ and T790M- patients with a baseline RECIST assessment and an evaluable response, T790M+ N=105 (from 107 T790M+
patients with response data; two patients not included as subgroup missing), T790M- N=50
Jänne, A#8009
50. AZD9291: Progression-free survival by
T790M (central test) status
0 6 12 18 24 30 36 42
Study week
Probabilityofprogression-freesurvival
T790M+ (95% CI)
T790M- (95% CI)
Dots indicate censored observations, shaded area represents 95% CIs; progression events that do not occur within
14 weeks of the last evaluable assessment (or first dose) are censored. Population: all dosed centrally confirmed T790M+
and T790M- patients, N=170 (115 T790M+, 55 T790M-; six patients for whom start date is not yet known are not included)
0
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
Patients at risk
T790M+
T790M-
115
55
96
33
78
21
56
15
21
7
6
0
1
0
Jänne, A#8009
51. Jänne, A#8009
AZD9291: Toxicity Summary
• No clear maximum-tolerated dose up to 240 mg/d
– No clear correlation of toxicity with dose
– 80 mg/d selected as optimal for therapeutic index
• At 80 mg/d dose:
– Diarrhea in 20%
– Rash in 27%
– Interstitial lung disease in 3%
– Hyperglycemia 1%
55. Current/Future Development of Third
Generation EGFR TKIs
• AZD9291
– AURA: Ph 2 expansion in T790M+
– AURA 2: Confirmatory Ph 2 in T790M+
– AURA 3: Ph 3 2nd line vs. chemo in T790M+
• CO-1686
– TIGER X: expansion of 2nd line or later in T790M+
– TIGER 1: Ph 2/3 1st line vs. erlotinib
(no T790M+ requirement)
– TIGER 2: Ph 2 after 1 prior EGFR TKI in T790M+
– TIGER 3: Ph 2 vs. chemo in T790M+
56. Summary of Third Generation
EGFR TKIs in Acquired Resistance
• BOTH agents have impressive efficacy and are
granted breakthrough designation by FDA
– Foot race to clinic
• Toxicity differences:
– AZD9291: rash & diarrhea (<erlotinib), ILD in minority
– CO-1686: hyperglycemia, mild diarrhea, nausea, rare
QTc prolongation
• Though some potential toxicity concerns in both,
anticipated benefit >> risk
• For both agents, focus is on T790M+ patients
58. No absolute rule for the amount of
evidence required to change practice
• Big effects don’t require big trials
• Crizotinib was justifiably approved based
on phase I/II trial with >50% RR
– Ceritinib similarly approved despite relatively small
numbers, but large effect
• EGFR TKI therapies became clear first line
standard of care despite absence of OS benefit
– Different standard for adding bevacizumab?
• Conversely, is an intervention clinically significant
if the trial needs >1000 patients to demonstrate
statistical significance?
59. In 2014, Cost/Value of Therapy is a
Factor in Cancer Care
• Reality is that cost matters, especially as new
drugs have eclipsed the prior $10,000/mo barrier
• It is appropriate to expect a semblance of value
and not merely p < 0.05
• We need to discuss value openly and not just
have it bias our clinical judgment
• Cost is limiting our ability to deliver best treatment
Optimal Rx
($$$$) Cost/practical
limits
Drug delivery
to needy patients
60. Take Home Messages for Advanced
NSCLC Management from ASCO 2014
• Necitumumab: Re-FLEX?; not enough benefit vs. toxicity
• Ramicirumab for 2nd line: Maybe; is 1.4 mo med OS diff
worth cost?; improving OS is hard, esp in squam NSCLC
• Crizotinib >> chemo first line (RR & PFS) in ALK+
• Ceritinib highly active for criz-naïve or criz-resistant
ALK+(RR & PFS), & CNS activity, but toxicity challenging
• Afatinib OS benefit specific to Del 19; Unique to afatinib?
– Major differences between Del 19 and L858R populations
• Bevacizumab significantly improved PFS w/erlotinib for
EGFR mut’n pos-NSCLC
• AZD9291 and CO-1686 both very active in EGFR T790M+
acquired resistance after prior 1st gen EGFR TKI